15-Hydroxy-eicosatetraenoic acid arrests growth of colorectal cancer cells via a peroxisome proliferator-activated receptor gamma-dependent pathway

George G. Chen, Hu Xu, Janet F.Y. Lee, Malayannan Subramaniam, Ka L. Leung, Su H. Wang, Ursula P.F. Chan, Thomas C. Spelsberg

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) inhibits cell growth via promoting apoptosis. Human colorectal cancer tissues had abundant PPARγ but the incidence of apoptosis was very low, suggesting a defect in the PPARγ pathway. Here, we found that 15-hydroxy-eicosatetraenoic acid (15S-HETE), an endogenous ligand for PPARγ, was significantly decreased in the serum of patients with colorectal cancer. Treatment of colon cancer cells with 15S-HETE inhibited cell proliferation and induced apoptosis, which was preceded by an increase in TGF-β-inducible early gene (TIEG) and a decrease in Bcl-2. The action of 15S-HETE could be blocked when PPARγ was suppressed. Overexpression of Bcl-2 prevented the apoptosis. The levels of TIEG and 15-lipoxygenase (15-LOX), the enzyme responsible for 15S-HETE production, was decreased in colorectal cancer. Therefore, colorectal cancer is associated with decreased 15S-HETE. Treatment of colon cancer cells with 15S-HETE inhibits cell proliferation and induces apoptosis in a PPARγ-dependent pathway involving augmentation of TIEG and reduction of Bcl-2 expression.

Original languageEnglish (US)
Pages (from-to)837-843
Number of pages7
JournalInternational Journal of Cancer
Volume107
Issue number5
DOIs
StatePublished - Dec 10 2003

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Keywords

  • 15-hydroxy-eicosatetraenoic acid
  • 15-lipoxygenase
  • Colorectal carcinoma
  • Peroxisome proliferator-activated receptor gamma
  • TGF-β-inducible early gene and Bcl-2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Chen, G. G., Xu, H., Lee, J. F. Y., Subramaniam, M., Leung, K. L., Wang, S. H., Chan, U. P. F., & Spelsberg, T. C. (2003). 15-Hydroxy-eicosatetraenoic acid arrests growth of colorectal cancer cells via a peroxisome proliferator-activated receptor gamma-dependent pathway. International Journal of Cancer, 107(5), 837-843. https://doi.org/10.1002/ijc.11447